Cellular senescence as a tumor-suppressor mechanism

Campisi, Judith

doi:10.1016/s0962-8924(01)82148-6

Cited by 371 publications

(32 citation statements)

References 29 publications

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“…The tumor suppression role of cellular senescence has been convincingly established in vitro (Bringold & Serrano 2000, Campisi 2001, Mooi & Peeper 2006, but further evidence is still needed to demonstrate the relationship between in vivo senescence and proliferation control (Mooi & Peeper 2006, Collado & Serrano 2010. In this context, benign pituitary microadenomas are faithful models of in vivo senescence (Mooi 2009, Chesnokova & Melmed 2010.…”

Section: Discussionmentioning

confidence: 99%

Evidence of cellular senescence during the development of estrogen-induced pituitary tumors

Sabatino

Petiti

Sosa

et al. 2015

Endocrine-Related Cancer

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Although pituitary adenomas represent 25% of intracranial tumors, they are usually benign, with the mechanisms by which these tumors usually avoid an invasive profile and metastatic growth development still remaining unclear. In this context, cellular senescence might constitute a plausible explanation for the benign nature of pituitary adenomas. In this study, we investigated the emergence of cellular senescence as a growth control mechanism during the progression of estrogen-induced pituitary tumors. The quantification of Ki67-immunopositive cells in the pituitaries of estrogenized male rats after 10, 20, 40, and 60 days revealed that the mitogenic potential rate was not sustained for the whole period analyzed and successively decreased after 10 days of estrogen exposure. In addition, the expression of cellular senescence features, such as the progressive rise in the enzymatic senescenceassociated b-galactosidase (SA-b-gal) activity, IL6, IL1b, and TGFb expression, was observed throughout pituitary tumor development. Furthermore, tumoral pituitary cells also displayed nuclear pATM expression, indicating activated DNA damage signaling, with a significant increase in p21 expression also being detected. The associations among DNA damage signaling activation, SA-b-gal expression, and p21 may provide a reliable combination of senescence-associated markers for in vivo pituitary senescence detection. These results suggest a role for this cellular process in the regulation of pituitary cell growth. Thus, cellular senescence should be conceived as a contributing component to the benign nature of pituitary adenomas, thereby influencing the capability of the pituitary gland to avoid unregulated cell proliferation.

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Section: Discussionmentioning

confidence: 99%

Evidence of cellular senescence during the development of estrogen-induced pituitary tumors

Sabatino

Petiti

Sosa

et al. 2015

Endocrine-Related Cancer

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“…The role of senescence in the aging of adult stem cells is tightly linked to tissue maintenance and homeostasis and often viewed as an irreversible barrier to immortalization and tumorigenesis under the assumption that senescence evolved to suppress tumorigenesis. 68, 69 This view has been intensely debated in recent years. 70, 71 Contrary to the hypothesis that senescence and tumorigenicity are always permanently connected and mutually exclusive, recent data monitoring p16INK4a in mice indicate that the activation of this hallmark of senescence is, in fact, a characteristic of all emerging cancers, 72 thus suggesting that cellular senescence might be a quasi-stable and/or plastic cellular state prone to cancerogenesis rather than a cancer preventive mechanism.…”

Section: Discussionmentioning

confidence: 99%

Opposing activities of oncogenic MIR17HG and tumor suppressive MIR100HG clusters and their gene targets regulate replicative senescence in human adult stem cells

et al. 2017

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Growing evidence suggests that many diseases of aging, including diseases associated with robust changes and adipose deports, may be caused by resident adult stem cell exhaustion due to the process called cellular senescence. Understanding how microRNA pathways can regulate cellular senescence is crucial for the development of novel diagnostic and therapeutic strategies to combat these pathologies. Herein, using integrated transcriptomic and semi-quantitative proteomic analysis, we provide a system level view of the regulation of human adipose-derived stem cell senescence by a subset of mature microRNAs (termed senescence-associated-microRNAs) produced by biogenesis of oncogenic MIR17HG and tumor-suppressive MIR100HG clusters. We demonstrate functional significance of these mature senescence-associated-microRNAs in the process of replicative senescence of human adipose-derived stem cells ex-vivo and define a set of senescence-associated-microRNA gene targets that are able to elicit, modulate and, most importantly, balance intimate connections between oncogenic and senescent events.

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“…Cancer is a multistep process of mutation, selection and clonal expansion [9], which relies on extensive cell proliferation and the progressive accumulation of mutations as cells divide. Replicative senescence is believed to have evolved as a tumour suppressor mechanism that limits cell proliferation and thus helps to prevent cancer [10]. By repressing telomerase expression, cells allow their telomeres to shorten with each cell division until they are exhausted and senescence is triggered.…”

Section: Introduction (A) Telomeres Replicative Senescence and Cancermentioning

confidence: 99%

All's well that ends well: why large species have short telomeres

Risques

Promislow

2018

Phil. Trans. R. Soc. B

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Among mammal species, almost all life-history traits are strongly size dependent. This size dependence even occurs at a molecular level. For example, both telomere length and telomerase expression show a size-dependent threshold. With some exceptions, species smaller than approximately 2 kg express telomerase, while species larger than that do not. Among species greater than approximately 5 kg, telomeres tend to be short-less than 25 kb-while among smaller species, some species have short and some have long telomeres. Here, we present a model to explore the role of body size-dependent trade-offs in shaping this threshold. We assume that selection favours short telomeres as a mechanism to protect against cancer. At the same time, selection favours long telomeres as a protective mechanism against DNA damage and replicative senescence. The relative importance of these two selective forces will depend on underlying intrinsic mortality and risk of cancer, both of which are size-dependent. Results from this model suggest that a cost-benefit model for the evolution of telomere length could explain phylogenetic patterns observed within the Class Mammalia. In addition, the model suggests a general conceptual framework to think about the role that body size plays in the evolution of tumour suppressor mechanisms.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.

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Cellular senescence as a tumor-suppressor mechanism

Cited by 371 publications

References 29 publications

Evidence of cellular senescence during the development of estrogen-induced pituitary tumors

Evidence of cellular senescence during the development of estrogen-induced pituitary tumors

Opposing activities of oncogenic MIR17HG and tumor suppressive MIR100HG clusters and their gene targets regulate replicative senescence in human adult stem cells

All's well that ends well: why large species have short telomeres

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